Abstract

ODSH, a new chemical entity, is 2-0, 3-0 desulfated heparin, a desulfated heparin analog that has been shown to bind to the receptor for advanced glycation endproducts (RAGE). This interaction prevents RAGE from binding to a principal ligand, HMGB1, as well as to other ligands including S-100 calgranulin, which attenuates the activation of RAGE. RAGE activation is known to induce resistance to chemotherapy and promote pancreatic tumor cell survival. We have shown, in vivo, an increase in response with gemcitabine when combined with ODSH. ODSH was tested alone and in combination with standard of care agent, gemcitabine, against BxPC-3 human pancreatic tumor xenograft model. Single agent ODSH and gemcitabine treatment showed an 18.8% and 16.8% decrease in tumor weight, respectively. The combination regimen of ODSH and gemcitabine increased tumor growth inhibition to 37.9%. This decrease was statistically significant (P<0.05) compared to ODSH and gemcitabine treatments alone according to Student's t-test. We believe this is a novel approach to treat metastatic pancreatic cancer. ODSH has already shown a favorable safety profile in Phase I and II studies. A clinical trial with ODSH treatment in combination with gemcitabine+nab-paclitaxel in newly diagnosed patients with metastatic pancreatic cancer is underway.